Type I allergy is an inflammatory response which is elicited as the invasion of exogenous agents into the body triggers release of various enzymes and chemical mediators, such as histamine and leukotrienes, from mast cells and eosinophils, which in turn induce tissue-damaging inflammations. The allergic response, when generalized, can lead to a systemic and often life threatening reaction known as anaphylactic shock.
The agents which trigger an anaphylactic shock response include various drugs such as penicillin and insulin, sources of desensitizing allergens such as ticks and fungi, dietary allergens such as eggs and peanuts, iodine-containing contrast media, local anesthetics and so on.
The current pharmacotherapy for anaphylactic shock consists in the administration of epinephrine and steroids. It is reported that if early therapy be judiciously instituted, the prognosis of this condition is generally satisfactory. However, these current treatments are no more than symptomatic remedies and the prophylaxis of anaphylactic shock is considered to be truly important. However, there is no established prophylactic modality for anaphylactic shock, and the current clinical practice appears to be based, at best, on the vague concept of preventing the invasion of high-risk foreign agents.
Therefore, in patients requiring certain drugs, such as penicillin and other antibiotics, and in cases in which an iodine contrast medium is used in X-ray diagnosis, these agents are administered of necessity, even knowing the attendant risk of anaphylactic shock. Thus, there is a pressing need for a positive prophylactic measure against such vigorous immune system responses.
In pollen allergy, symptoms occur preferentially in the nose and eye. Recent years have witnessed a rapid increase in the number of patients who complain of the so-called pollinosis symptoms due to pollens of cedar and other allergenic plants, resulting in, for example, allergic conjunctivitis and allergic rhinitis (eye watering, sinus congestion, nasal congestion, sneezing and the like).
For the prevention of pollen disease, a prophylactic treatment with antiallergic agents, a symptomatic treatment with antihistamines and steroids, and hyposensitization therapy are generally indicated.
However, there is not available as yet an antiallergic agent effective enough as a preventive drug, while the antihistamines and steroids in current use for symptomatic treatment have the problem of side effects.
Atopy provides hereditary basis for allergic responses. The condition is revealed as a congenital hypersensitivity to specific agents, and is usually manifested as bronchial asthma and allergic rhinitis in the patient and his family.
Atopic dermatitis is an inflammatory disease of the skin, which may arise because of a predisposition and which is often characterized by areas of localized itch. It is also known that as the affected area is scratched, the local eruption is aggravated so that the disease runs a chronic course. Moreover, the pruritus associated with atopic dermatitis develops suddenly in many cases and tends to be provoked and intensified by the slightest stimulation.
A variety of treatments have been attempted for atopic dermatitis, but they have proved unsuccessful. The current therapeutic modality for this disease consists of the topical treatment primarily with topical adrenocorticoids and, as an adjunct therapy, antipruritic agents such as antihistamines. But since these drugs are not free from side effects, the advent of a safe and more sure-acting drug for the prevention and treatment of atopic dermatitis has been awaited in earnest.
Patients with bronchial asthma are rapidly increasing in number and presenting a serious problem everywhere in the world today. Bronchial asthma is an airway disease, the cardinal manifestation of which is respiratory distress due to paroxysmal airway constriction, which is life-threatening at times.
While many etiologic agents are usually involved in the onset of bronchial asthma, the chief cause is generally believed to be an increased airway responsiveness due to allergic factors associated with inhaled antigens such as ticks, pollens, dust and so on.
For the treatment of bronchial asthma, prophylaxis with antiallergic drugs and symptomatic treatment with .beta.-receptor stimulants and steroids are practiced today, but there is no antiallergic drug effective enough as a prophylactic. Further, the problem of side effects has been pointed out frequently with the use of .beta.-receptor stimulants and steroids used for symptomatic treatment.
A high affinity immunoglobulin E receptor (Fc.epsilon.RI) is a glycoprotein having a tetrameric structure consisting of an .alpha.-chain, a .beta.-chain and two disulfidized .gamma.-chains. It has been reported that a soluble fragment of Fc.epsilon.RI .alpha.-chain (sFc.epsilon.RI.alpha.) is produced by genetic engineering techniques using DHFR-deficient CHO cells and that only the extracellular region of the .alpha.-chain is involved in the high-affinity binding to IgE Blank, U. et al., J. Biol. Chem., 266, 2639 (1991)!.
Urea-denatured antigen E derived from pollen of Ambrosia and urea-denatured ovalbumin are known to inhibit production of IgE. These urea-denatured antigens inhibit the IgE production reaction by increasing suppressor T cells which suppress helper T cell activity to thereby prevent differentiation of B cells to antibody-producing cells. Suplatast tosilate is also known as a substance capable of inhibiting the IgE produciton. However, these substances have not been put to practical use due to side effects and other problems.
Further, it has not been known so far that peptides capable of binding to IgE directly act on B cells to prevent the IgE production in B cells.
In the development of a drug for the prevention and treatment of IgE-related diseases, a screening of candidate substances is of importance.
One approach to this end comprises inducing an IgE-mediated allergic reaction and checking to see how far this reaction is inhibited. Such approach includes a method comprising the use of animals subjected to passive immunization with purified IgE or animals subjected to active immunization with an antigen as model animals. Both methods are useful but not suited for inducing an allergic reaction repeatedly for investigating the inhibitory effect of test substances.
Thus, in the former method, IgE must be repeatedly administered in order that the allergic reaction may be induced in repetition, with the result that a drug screening cannot be expediently carried out.
The latter method is also disadvantageous in that even though an allergic reaction can be repeatedly induced, not only the antigen-specific IgE but also other antibodies such as the reaction-interfering antigen-specific IgG etc. are produced in the body so that the inhibitory effect on IgE-mediated allergic reaction cannot be accurately estimated.